W. L. Gore & Associates, Inc.

Patent Trials and Appeals Board

Mar 16, 2022

2021002294 (P.T.A.B. Mar. 16, 2022)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 15/632,233 06/23/2017 Steven M. Alston 450385.001974 1563US07 1986 133414 7590 03/16/2022 Faegre Drinker Biddle & Reath LLP - W.L. Gore 2200 Wells Fargo Center 90 South Seventh Street Minneapolis, MN 55402-3901 EXAMINER MERCIER, MELISSA S ART UNIT PAPER NUMBER 1615 NOTIFICATION DATE DELIVERY MODE 03/16/2022 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): patentdocketing@faegredrinker.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte STEVEN M. ALSTON, ELAZER R. EDELMAN, PETER HEICKSEN, THERESA A. HOLLAND, PETER M. MARKHAM, PETER D. TRAYLOR, ABRAHAM TZAFRIRI, and BRETT G. ZANI __________ Appeal 2021-002294 Application 15/632,233 Technology Center 1600 __________ Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and TAWEN CHANG, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to drug coated balloons where the drug coating layer comprises microcrystals in a haystack orientation. The Examiner rejected the claims as failing to comply with the enablement requirement. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as W. L. GORE & ASSOCIATES, INC. (see Appeal Br. 2). We have considered the Specification of June 23, 2017 (“Spec.”); Final Action of Apr. 28, 2020 (“Final Action”); Appeal Brief of Sept. 28, 2020 (“Appeal Br.”); Examiner’s Answer of Dec. 11, 2020 (“Ans.”); and Reply Brief of Feb. 11, 2021 (“Reply Br.”). Appeal 2021-002294 Application 15/632,233 2 Statement of the Case Background A “common treatment for vascular disease is the short-term or long- term contact of a tissue with an endovascular medical device, such as a balloon or a stent, respectively, that is coated with a drug that prevents or reduces vascular disease at the site of contact” (Spec. ¶ 3). “The dosing of the drug to the treatment site using DCBs [drug coated balloons] can be highly variable and unpredictable immediately after implantation or deployment, and local drug levels in the vascular tissue can be highly variable and unpredictable over an extended time” (id. ¶ 4). “[I]t has been demonstrated that the microcrystalline surface coating morphology comprising microcrystals in a haystack orientation may determine distribution of the drug on the inner surface of the blood vessel and in some manner may maximize tissue retention of the drug” (id. ¶ 89). The Claims Claims 1-3, 5-7, and 28-37 are on appeal. Claim 1 is an independent claim, is representative and reads as follows: 1. A medical device comprising: a balloon comprising an outer surface; and a drug coating layer on the outer surface of the balloon, wherein the drug coating layer comprises microcrystals in a haystack orientation having random and a substantial absence of uniformity in placement on the outer surface of the balloon. The Rejection The Examiner rejected claims 1-3, 5-7, and 28-37 under 35 U.S.C. § 112(a) for lack of enablement (Final Act. 2-6). Appeal 2021-002294 Application 15/632,233 3 The Examiner finds “[i]t is well known that crystal angles and formation on a substrate is unpredictable and uncontrollable” (Final Act. 4). The Examiner finds that: Because of the known unpredictability of the art . . . and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept the assertion that the instantly claimed drug coated balloon ha[ving] a “haystack orientation” as defined by Applicant could be predictably made as inferred in the claims. The skilled artisan would have to participate i[n] repeated hit or miss testing and experimentation with no expectation of obtaining a predictable and reproducible result. Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112, first paragraph. (id. at 5-6). Appellant contends the methods of Cleek,2 “which were known, specifically called out, and utilize readily available starting materials, would have provided ample guidance as a starting point from which to apply the specific teachings of the instant application” (Appeal Br. 7). The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner’s conclusion that the Specification does not enable the full scope of the claimed invention? Findings of Fact Breadth of Claims 1. The Examiner finds the claims are broad and “are not limited to a specific formulation of the coating, only the active agent within the drug coating layer is claimed” in claim 3, which is not an independent claim (Ans. 2 Cleek et al., US 2014/0271775 A1, published Sept. 18, 2014. Appeal 2021-002294 Application 15/632,233 4 4). 2. Claim 1 is reasonably interpreted as encompassing any drug (see Spec. ¶ 103 “The coating layer 750 may be comprised of at least one natural, semi-synthetic or synthetic therapeutic agent (e.g., at least one drug)”). 3. Claim 1 is reasonably interpreted as encompassing a coating layer comprising any functional solvent. The Specification teaches: In various embodiments, the formulation for the coating layer 750 comprises at least one therapeutic agent, an excipient, and a solvent. The choice of the solvent may be useful for the crystal morphology of the coating layer 750 in a dry state and adherence and release of the therapeutic agent from the surface of the medical device. Accordingly, the solvent may include acetone, dioxane, tetrahydrofuran (THF), water, and mixtures thereof. The choice of solvent must also consider toxicity and biocompatibility. (Spec. ¶¶ 108-109). 4. Claim 1 is reasonably interpreted as encompassing microcrystals in a haystack orientation resulting from any process of preparation. Indeed the Specification defines the term “microcrystals in a haystack orientation” below: A “microcrystal haystack” or the phrase “microcrystals in a haystack orientation” is defined as a plurality of microcrystals, the majority of which are oriented at less than a 20 degree angle from a surface on which they are positioned. In addition, the majority of the plurality of microcrystals each have a major (overall) dimension length that is at least five (5) times greater than the major (overall) dimension width of the microcrystal. (Spec. ¶ 78; emphasis added). See Helmsderfer v. Bobrick Washroom Equip., Inc., 527 F.3d 1379, 1381 (Fed. Cir. 2008) (“A patentee may act as Appeal 2021-002294 Application 15/632,233 5 its own lexicographer and assign to a term a unique definition that is different from its ordinary and customary meaning.”). Presence of Working Examples 5. The Specification teaches, in Example 2, that: Surprisingly, the fluoropolymer surface and a microcrystalline surface coating morphology of the PTX [paclitaxel] coated balloons (ePTFE - W.L. Gore, Flagstaff AZ) produced a 3.8- fold higher retainable drug delivery at 1 hour and a 1.6-fold higher retainable drug delivery at 1 day over that of the PTX coated balloons (Commercial). Moreover, the PTX coated balloons (ePTFE - W.L. Gore, Flagstaff AZ) showed no signs of particulation after inflation/deflation at a benchtop, whereas the PTX coated balloons (Commercial) demonstrated particulation. (Spec. ¶ 136). The Specification connects Example 2 to the claim by teaching “the results of DCBs with a fluoropolymer surface and a microcrystalline surface coating morphology comprising [paclitaxel] microcrystals in a haystack orientation provided a synergistic increase in tissue retention, as shown in . . . Example 2” (id. ¶ 91). 6. Figures 8A and 8B are reproduced below: Appeal 2021-002294 Application 15/632,233 6 According the the Specification, “Figures 8A and 8B show microcrystalline morphology on non-porous and porous balloon substrates in accordance with some aspects of the present disclosure” (Spec. ¶ 51). The Specification further states with respect to these figures: The microcrystalline morphology may comprise microcrystals 815 in a haystack orientation 820. For example, the microcrystals 815 may be uniformly distributed across the substrate, and demonstrate a random and a substantial absence of uniformity (non-uniform) in placement on the substrate and/or random and a substantial absence of uniformity (non- uniform) in angle of projection from the substrate. (Spec. ¶ 112). 7. The Specification provides no working examples for any drugs other than paclitaxel, does not disclose what solvent, if any, is used for paclitaxel, and does not provide an example of the specific process of coating the balloon. Amount of Direction or Guidance Presented 8. The Specification teaches the “drug coating layer may include microcrystals in a haystack orientation having random and a substantial absence of uniformity in placement on the outer surface of the balloon. . . . The drug coating may include paclitaxel” (Spec. ¶ 9). The Specification further explains the “coating layer may include a therapeutic agent, an excipient, and microcrystals in a haystack orientation having random and a substantial absence of uniformity in placement on an outer surface of the polymeric layer” (id. ¶ 12). 9. The Specification teaches the therapeutic agent comprises paclitaxel, a taxane, docetaxel, vinca alkaloids, colchicine, podophyllotoxin, griseofulvin, anti- Appeal 2021-002294 Application 15/632,233 7 mitotic alkaloid agents anti-microtubule alkaloid agents, protaxel, arsenic trioxide, thalidomide, atorvastatin, cerivastatin, fluvastatin, betamethasone diproprionate, dexamethasone 21-palmitate, sirolimus, everolimus, zotarolimus, biolimus or temsirolimus. As should be understood the at least one therapeutic agent may include structural analogs, related substances, degradants. and derivatives of any of the afore-mentioned drugs. (Spec. ¶ 104). The Specification provides no information regarding whether any of these drug compounds form crystals, and if they do form crystals, whether the crystals would possess a dimension length that is five times greater than the dimension width of the microcrystal. 10. Dr. Theresa Holland states: It is my opinion that one skilled in the art would understand the specific descriptions of the balloon 700 and coating layer 750 in at least paragraphs 93, 95, and 96 [of the Specification] as providing examples of formulations that would result in a drug coated balloon having drug crystals contained in a haystack orientation. (Holland Decl.3 ¶ 14). The Specification teaches, in these cited paragraphs, that a medical balloon 700 may further comprise a balloon wall 720 comprising an outer surface 725 and an inner surface 727. The balloon wall 720 defines a chamber 730 and may be constructed of a layered material 735. In some embodiments, the layered material 735 comprises a thermoplastic polymeric layer 740 at 3 Declaration of Theresa Holland under 37 C.F.R. § 1.132 (Apr. 6, 2020) (Holland Declaration). Appeal 2021-002294 Application 15/632,233 8 least partially adhered to a substrate or polymeric layer 745 in an overlying relationship to each other. (Spec. ¶ 93). The Specification teaches a coating layer 750 (e.g., a drug coating) is distributed evenly across at least a portion of the outer surface 725 of the layered material 735. For example, as shown in FIGS. 7B, 7C, and 7D, a coating layer 750 may be distributed evenly across at least a portion of the outer surface of the polymeric layer 745. In some embodiments, the coating layer 750 is distributed evenly across only substantially the working length of the balloon 700. In other embodiments, the coating layer 750 is distributed evenly across substantially the working length of the balloon 700 and at least a portion of the leg portions 705 and/or shoulder/tapered portions 710. (Spec. ¶ 95). The Specification teaches the coating layer 750 does not penetrate into a polymeric layer 745 having a non-porous microstructure, and thus would be fully disposed on the outermost layers (e.g., outer two layers) of a non-porous microstructure cover (e.g., Nylon). Accordingly, without being bound by theory, a polymeric layer 745 having a porous microstructure, such as ePTFE, provides a sponge-like scaffold for the coating layer 750 (e.g., paclitaxel/stearic acid/tris coating) with a coating penetration to a depth of about 5 μm. (Spec. ¶ 96). Relative skill in the art 11. The Examiner and Appellant appear to agree that the skill in the art is high (see Final Act. 4; Appeal Br. 5). State of the Prior Art and Unpredictability of the Art 12. Cleek teaches “a composite material can comprise a plurality of high aspect ratio paclitaxel crystals extending at least partially into said porous substrate and optionally projecting from a porous substrate at an Appeal 2021-002294 Application 15/632,233 9 angle of at least 20 to 90 degrees relative to the substrate” (Cleek ¶ 22). 13. Cleek teaches, in Example 4, that: This example describes the general procedure for the preparation of drug crystals onto a substrate using solvent evaporation. Paclitaxel (LC Laboratories, Boston Mass.) was dissolved at room temperature by stirring into methanol (ACS grade, Aldrich), acetonitrile (ACS grade, Aldrich), acetone (ACS grade, Aldrich), or chloroform (reagent grade, Sigma), at a concentration of 10 to 30 mg/ml, optionally containing urea (reagent grade, Sigma) at a mass ratio of 1:1 to 8:1 (paclitaxel:urea). 50 to 500 µl of the paclitaxel solution was then cast onto the substrates of Examples 1 through 3, by depositing the solution from a pipettor over the surface area of the ePTFE or nylon substrates. The samples were air-dried in a laminar fume hood at about 20° C. at an ambient atmospheric pressure of about 773 mm Hg to cause the solvent to evaporate. (The paclitaxel solution can be applied to the substrate in a variety of ways including pipetting, dipping, spraying, brushing, and the like.) (Cleek ¶¶ 102-103). 14. Cleek teaches “the ex vivo transfer of drug crystals from an ePTFE substrate to a vascular tissue” where a substrate with “high aspect paclitaxel crystal habits embedded and oriented in the ePTFE microstructure” was treated “to expose the endothelial layer to the paclitaxel crystals. The endothelial layer was compressed at about 5.4 atm against the coated ePTFE substrate for 60 sec” and the endothelial layer was “extensively covered with engaged and embedded paclitaxel crystals, indicating transfer from the ePTFE substrate to the vascular tissue” (Cleek ¶¶ 123-127). Appeal 2021-002294 Application 15/632,233 10 15. Figures 5 and 6 of Cleek are reproduced below: As seen in FIG. 5, paclitaxel 500 coated onto nylon 502 from acetonitrile solvent (10 mg/ml) produced a smooth, continuous coating, absent of any high aspect ratio habits. As seen in FIG. 6, paclitaxel coated onto nylon from methanol solvent (10 mg/ml) produced a plurality of aggregates of paclitaxel crystals comprising high aspect ratio habits. The aggregates were observed to be adherent to the nylon substrate, but did not penetrate or otherwise embed into the bulk of the nylon substrate. (Cleek ¶ 105). Principles of Law When rejecting a claim under the enablement requirement of section 112, the PTO bears an initial burden of setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application. In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). Factors to be considered in determining whether a disclosure would require undue experimentation … include (1) the Appeal 2021-002294 Application 15/632,233 11 quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Analysis “The requirement of enablement, stated in 35 U.S.C. § 112, enforces the essential ‘quid pro quo of the patent bargain’ by requiring a patentee to teach the public how ‘to practice the full scope of the claimed invention.’” Pacific Biosciences California, Inc. v. Oxford Nanopore Tech., Inc., 996 F.3d 1342, 1350 (Fed. Cir. 2021) (citing McRO, Inc. v. Bandai Namco Games America Inc., 959 F.3d 1091, 1096 (Fed. Cir. 2020). “[A] patentee chooses broad claim language at the peril of losing any claim that cannot be enabled across its full scope of coverage.” MagSil Corp. v. Hitachi Glob. Storage Techs., Inc., 687 F.3d 1377, 1381 (Fed. Cir. 2012). Applying the Wands factors to the evidence of record, we find that Appellant has not provided a disclosure that is enabling commensurate in scope with the breadth of the claims. The claims broadly encompass a balloon having a drug coating layer comprising microcrystals in a haystack orientation. When Appellant’s express definition of “microcrystals in a haystack orientation” is incorporated into claim 1, claim 1 further requires microcrystals at less than a 20 degree angle with a dimension length that is five times greater than the dimension width of the microcrystal (FF 1-4). Appeal 2021-002294 Application 15/632,233 12 While Appellant asserts that there are four examples (Appeal Br. 9), these examples are limited to paclitaxel and do not recite any specific solvent or process conditions to obtain microcrystals in a haystack orientation with less than a 20 degree angle with a dimension length that is five times greater than the dimension width of the microcrystal (FF 5-7). We recognize Appellant’s arguments that: “If the skilled artisan were to execute on these Examples, they would observe the haystack orientation” (Appeal Br. 9), but we are not persuaded that sufficient information is given in the Specification to reproduce these examples. Appellant points to paragraph 126 to 148 of the Specification that are limited to paclitaxel, but Appellant does not point to any disclosure in these examples that identifies what solvent and conditions were used to result in crystallization. Nor does Appellant provide any reasoned or scientific basis for concluding that whatever undefined conditions function with paclitaxel would have any expectation for functioning with other drug compounds. And while the Specification recites a few solvents (FF 3) and drug compounds (FF 9), the Specification also does not identify which drug compounds will crystallize, in which solvents, and if they will crystallize, whether they will crystallize in the proper haystack orientation with the correct dimensions (FF 9). Nor does the Specification provide generic disclosure of process conditions for forming crystals within the scope of the claims (see Spec. generally; FF 8- 10). We have also considered the Holland Declaration, but Dr. Holland does not identify any evidence supporting her statement that: It is my opinion that one skilled in the art would understand the specific descriptions of the balloon 700 and coating layer 750 in Appeal 2021-002294 Application 15/632,233 13 at least paragraphs 93, 95, and 96 as providing examples of formulations that would result in a drug coated balloon having drug crystals contained in a haystack orientation. (Holland Decl. ¶ 14). We give the Holland Declaration minimal weight because the cited portions of the Specification, reproduced in FF 10 above, provide no substantive disclosure of what conditions are necessary to crystallize paclitaxel into the required form, much less the broad scope of claim 1 that encompasses crystallizing all other drugs. Nor does the Holland Declaration provide any evidence that the Specification discloses, or that an ordinary artisan would have been able to identify, which drugs will crystallize, or not, and which of these crystals will allow the ordinary artisan to obtain microcrystals in a haystack orientation with less than a 20 degree angle with a dimension length that is five times greater than the dimension width of the microcrystal as required by claim 1. We therefore conclude that the Holland Declaration is, like the Specification, substantially deficient in disclosure and does not persuasively establish that the ordinary artisan would “possess sufficient information to manufacture of a balloon with and a drug coating layer (with microcrystals in a haystack orientation having random and a substantial absence of uniformity in placement on the outer surface of the balloon)” (Holland Decl. ¶ 16). See In re American Academy of Science Tech Center, 367 F.3d 1359, 1370 (Fed. Cir. 2004) (“[T]he Board is entitled to give such weight to declarations as it deems appropriate.”) As to unpredictability, Appellant asserts “all the methods needed to practice the haystack configuration of the claimed device were well known in the art as evidenced at least by Cleek” (Appeal Br. 6). Appellant contends Appeal 2021-002294 Application 15/632,233 14 “that Cleek’s methods, which were known, specifically called out, and utilize readily available starting materials, would have provided ample guidance as a starting point from which to apply the specific teachings of the instant application” (id. at 7). Appellant contends the minimum of Cleek’s disclosed range (about 20 degrees) clearly approaches the maximum of the instant range, less than 20 degrees. It follows that one skilled in the art armed with the present disclosure and Cleek’s disclosure would almost, if not immediately, know that Cleek’s methods would be a starting point from which to derive similar products to those but in the instant range. (id. at 8). We are not persuaded. While Cleek does, at least, disclose some particular conditions that result in preparation of paclitaxel drug crystals including solvent, temperature, and drying procedure (see FF 13-15), Cleek does not provide an example for any other drug crystal and Cleek does not persuasively show, or provide persuasive reasoning, that the disclosed process for making paclitaxel crystals would produce crystals having the claimed orientation for any other drug. Thus, Cleek does not address the concern that undue experimentation would have been required to prepare drug crystals commensurate in scope with claim 1. Also, Cleek expressly teaches “an angle of at least 20 to 90 degrees relative to the substrate” (FF 12) and broadens it slightly with “about 20”, but that does not provide enablement for the full scope of claim 1, as constrained by Appellant serving as lexicographer to require “less than a 20 degree angle” (FF 4). That is, even if an angle of “about 20 to 90” degrees in Cleek and “less than a 20 degree angle” in claim 1 overlap, and there is thus very limited support for paclitaxel crystals with, e.g., 19.5 degrees, that Appeal 2021-002294 Application 15/632,233 15 does not enable the full scope of claim 1 encompassing any value that is “less than a 20 degree angle” including 1, 5, 10, or 15 degrees. Indeed, rather than the support the enablement of the claim, Cleek’s process more practically does not, in general, produce a paclitaxel composition within the scope of claim 1. Cleek suggests that the process produces a product with greater angles from 20 to 90 degrees (FF 12). Cleek therefore supports the Examiner’s reasoning by showing that the only process actually disclosed on the record does not produce compositions commensurate in scope with claim 1. Appellant does not identify specific enabled teachings in Cleek that explain or exemplify how to crystalize drugs other than paclitaxel with the required haystack orientation (see Appeal Br. generally). Indeed, Appellant provides no disclosure in the Specification, and does not particularly identify a disclosure in Cleek, that teaches how to obtain a paclitaxel composition where the majority of microcrystals “are oriented at less than a 20 degree angle from a surface on which they are positioned” (FF 4). There is no disclosure as to how to obtain such microcrystals at such angles for any other drug, and no disclosure of processes to do so. It is based on the absence of any disclosure, examples, and unpredictability in crystallization, that the Examiner finds that undue experimentation would have been required to make the full scope of the claimed product (see Ans. 4). Finally, the Specification itself suggests that the process is unpredictable when teaching regarding Example 2 that: “Surprisingly, the fluoropolymer surface and a microcrystalline surface coating morphology of the PTX coated balloons . . . produced a 3.8-fold higher retainable drug Appeal 2021-002294 Application 15/632,233 16 delivery at 1 hour and a 1.6-fold higher retainable drug delivery at 1 day over that of the PTX coated balloons” (FF 5). That the result is surprising suggests that the ordinary artisan would not have found it predictable or obvious to reproduce the Example 2 surprising result. And since the Specification does not provide the conditions for crystalizing microcrystals generally, or even paclitaxel specifically, to obtain this result, it would have been unpredictable and require undue experimentation to reproduce this result as it would require testing many different solvents at many different temperature and crystallization conditions without guidance in order to obtain the surprising result. Therefore, as we balance the high level of skill in the art (FF 11) against the very broad scope of the claims, the essentially absent teachings regarding the processes for crystalizing drugs other than paclitaxel into the haystack orientation (and absence of teachings on how to crystalize even paclitaxel into a haystack orientation with “less than a 20 degree angle”), the very limited set of working examples that solely focus on paclitaxel, the unpredictability of crystallizing any drug whatsoever using any conditions whatsoever, and the large quantity of experimentation that would be necessary to develop such methods, we conclude that undue experimentation would have been required to make the drug coated balloons as claimed. Conclusion of Law A preponderance of the evidence of record supports the Examiner’s conclusion that the Specification does not enable the full scope of the claimed invention. Appeal 2021-002294 Application 15/632,233 17 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-3, 5-7, 28-37 112(a) Enablement 1-3, 5-7, 28-37 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED